Asymmetric carbomagnesation

The chemistry described in this review article demonstrates the impressive positive influence that catalytic RCM has had on our research in connection to the development of other catalytic and enantioselective C-C bond forming reactions. There is no doubt that in the absence of pioneering work by Schrock and Grubbs, the Zr-catalyzed alkylation and kinetic resolution would be of less utility in synthesis. The number of unsaturated heterocyclic and carbocyclic substrates available for Zr-catalyzed asymmetric carbomagnesation would be far more limited without catalytic RCM. 

Because of the availability of the chiral catalyst 31, it was obvious to investigate the enantioselective carbomagnesation of prochiral substrates. Hoveyda and co-workers demonstrated that asymmetric carbomagnesations of cyclic allylic... 

Detailed studies in these laboratories have shed light on the mechanistic intricacies of asymmetric catalytic carbomagnesations, allowing for an understanding of the above trends in regio- and stereoselectivity [9]. Importantly, these mechanistic studies have indicated that there is no preference for the formation of either the anti or the syn (ebthi)Zr—alkene isomers (e. g. 8 anti vs. 8 syn) it is only that one metallocene—alkene... 

As depicted in Eqs. 6.5—6.7, kinetic resolution of a variety of cyclic allylic ethers is effected by asymmetric Zr-catalyzed carbomagnesation. Importantly, besides six-membered ethers, seven- and eight-membered ring systems can readily be resolved by the Zr-catalyzed protocol. 

As depicted in Eqs (3)-(5), kinetic resolution of a variety of cyclic allylic ethers is effected by asymmetric Zr-catalyzed carbomagnesation. Importantly, in addition to six-membered ethers, seven- and eight-membered ring systems can be readily resolved by the Zr-catalyzed protocol. It is worthy of note that the powerful Ti-catalyzed asymmetric epoxidation procedure of Sharpless [15] is often used in the preparation of optically pure acyclic allylic alcohols through the catalytic kinetic resolution of easily accessible racemic mixtures [16]. When the catalytic epoxidation is applied to cyclic allylic substrates, reaction rates are retarded and lower levels of enantioselectivity are observed. Ru-catalyzed asymmetric hydrogenation has been employed by Noyori to effect resolution of five-... 

The high levels of enantioseicctivity obtained in the asymmetric catalytic carbomagnesation... 

Zirconocene-catalyzed carbomagnesation of internal allylic ethers proceeds by a different pathway. The carbometallation of allylic ethers with the internal double bond gives formally the S 2 substitution product 15 with the loss of the ether moiety (Scheme 7). A few examples are given in Table 4. Especially interesting, from the synthetic point of view, is ethylmagnesation of cyclic ethers (the last entry in Table 4), because it opens a pathway to the synthesis of functionalized homoallylic alcohols [14]. An asymmetric variant of this reaction gives products with ees>90% [15]. 

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